Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVDMHSY)

• DOT Name: Trichoplein keratin filament-binding protein (TCHP)
• Synonyms: Protein TCHP; Mitochondrial protein with oncostatic activity; Mitostatin; Tumor suppressor protein
• Gene Name: TCHP
• Related Disease:
  Gastric cancer
  Meningioma
  Acute leukaemia
  Adult glioblastoma
  Advanced cancer
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Cardiovascular disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Head and neck cancer
  Head and neck carcinoma
  Kidney cancer
  Multiple endocrine neoplasia type 1
  Myocardial infarction
  Neurofibromatosis type 2
  Ovarian cancer
  Ovarian neoplasm
  Progressive multifocal leukoencephalopathy
  Proliferative vitreoretinopathy
  Promyelocytic leukaemia
  Renal carcinoma
  Renal cell carcinoma
  Bloom syndrome
  Carcinoma
  Familial adenomatous polyposis
  Lung adenocarcinoma
  Plasma cell myeloma
  Head-neck squamous cell carcinoma
  Invasive ductal breast carcinoma
  Kaposi sarcoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Melanoma
  Non-small-cell lung cancer
  Squamous cell carcinoma
  Stomach cancer
  T-cell acute lymphoblastic leukaemia
• UniProt ID: TCHP_HUMAN
• Pfam ID: PF13868
• Sequence:
  MALPTLPSYWCSQQRLNQQLARQREQEARLRQQWEQNSRYFRMSDICSSKQAEWSSKTSY
  QRSMHAYQREKMKEEKRRSLEARREKLRQLMQEEQDLLARELEELRLSMNLQERRIREQH
  GKLKSAKEEQRKLIAEQLLYEHWKKNNPKLREMELDLHQKHVVNSWEMQKEEKKQQEATA
  EQENKRYENEYERARREALERMKAEEERRQLEDKLQAEALLQQMEELKLKEVEATKLKKE
  QENLLKQRWELERLEEERKQMEAFRQKAELGRFLRHQYNAQLSRRTQQIQEELEADRRIL
  QALLEKEDESQRLHLARREQVMADVAWMKQAIEEQLQLERAREAELQMLLREEAKEMWEK
  REAEWARERSARDRLMSEVLTGRQQQIQEKIEQNRRAQEESLKHREQLIRNLEEVRELAR
  REKEESEKLKSARKQELEAQVAERRLQAWEADQQEEEEEEEARRVEQLSDALLQQEAETM
  AEQGYRPKPYGHPKIAWN
• Function: Tumor suppressor which has the ability to inhibit cell growth and be pro-apoptotic during cell stress. Inhibits cell growth in bladder and prostate cancer cells by a down-regulation of HSPB1 by inhibiting its phosphorylation. May act as a 'capping' or 'branching' protein for keratin filaments in the cell periphery. May regulate K8/K18 filament and desmosome organization mainly at the apical or peripheral regions of simple epithelial cells. Is a negative regulator of ciliogenesis.
• Tissue Specificity: Expressed at high levels in normal urothelial and breast epithelial cells. Also expressed in the smooth muscle and endothelial cells. Reduced expression seen in advanced bladder and breast carcinomas (at protein level). Ubiquitous. Expressed at highest levels in the heart, skeletal muscle, kidney, liver and testis.

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Posttranslational Modification	[1]
Meningioma	DISPT4TG	Definitive	Genetic Variation	[2]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Cardiac failure	DISDC067	Strong	Biomarker	[9]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[15]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[16]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[17]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[17]
Kidney cancer	DISBIPKM	Strong	Altered Expression	[11]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Genetic Variation	[18]
Myocardial infarction	DIS655KI	Strong	Biomarker	[9]
Neurofibromatosis type 2	DISI8ECS	Strong	Altered Expression	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[15]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[15]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[20]
Proliferative vitreoretinopathy	DISZTEK1	Strong	Biomarker	[21]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[20]
Renal carcinoma	DISER9XT	Strong	Altered Expression	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[22]
Bloom syndrome	DISKXQ7J	moderate	Biomarker	[23]
Carcinoma	DISH9F1N	moderate	Biomarker	[24]
Familial adenomatous polyposis	DISW53RE	moderate	Biomarker	[25]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[26]
Plasma cell myeloma	DIS0DFZ0	moderate	Genetic Variation	[27]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[28]
Invasive ductal breast carcinoma	DIS43J58	Limited	Biomarker	[29]
Kaposi sarcoma	DISC1H1Z	Limited	Posttranslational Modification	[30]
leukaemia	DISS7D1V	Limited	Biomarker	[31]
Leukemia	DISNAKFL	Limited	Biomarker	[31]
Lung cancer	DISCM4YA	Limited	Biomarker	[32]
Lung carcinoma	DISTR26C	Limited	Biomarker	[32]
Melanoma	DIS1RRCY	Limited	Biomarker	[33]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[34]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[35]
Stomach cancer	DISKIJSX	Limited	Posttranslational Modification	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[36]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Trichoplein keratin filament-binding protein (TCHP).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Trichoplein keratin filament-binding protein (TCHP).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Trichoplein keratin filament-binding protein (TCHP).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Trichoplein keratin filament-binding protein (TCHP).	[40]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Trichoplein keratin filament-binding protein (TCHP).	[42]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Trichoplein keratin filament-binding protein (TCHP).	[44]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Trichoplein keratin filament-binding protein (TCHP).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Trichoplein keratin filament-binding protein (TCHP).	[43]

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